The natural diseases of New Zealand Black mice and their hybrids with the New Zealand White strain are under investigation by genetic, immunologic, and virologic procedures. These diseases comprise multifactorial immune-complex glomerulonephritis, a model of human systemic lupus erythematosus; autoimmune hemolytic anemia, a model of human autoantibody-mediated anemia; and malignant lymphoma or leukemia. The natural history of the murine disease is characterized by endogenous type-C viral envelope glycoprotein antigenemia and pathogenetic antibody responses both to endogenous viral proteins and to self antigens. The objective of this project is to elucidate the genetic, viral, and immunological determinants of disease in the animal model and to gain insight by parallel studies into the nature of corresponding human diseases, particularly systemic lupus and leukemia.